AB0939 BONE-RELATED OUTCOME DURING TWO YEARS OF SECUKINUMAB TREATMENT IN PATIENTS WITH ANKYLOSING SPONDYLITIS: RADIOGRAPHIC SPINAL AND FACET INVOLVEMENT, BONE MINERAL DENSITY, VERTEBRAL FRACTURES AND BONE TURNOVER MARKERS
Authors: M. Siderius, S. Arends, F. Wink, A. Spoorenberg
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> IL17 inhibitors have proven to reduce disease activity in patients with ankylosing spondylitis (AS). AS is an intriguing disease which is characterized by both excessive bone formation and bone loss. Data on the effect of IL17 inhibitors on the different aspects of bone formation as well as bone resorption is still limited. <h3>Objectives</h3> To evaluate radiographic progression of the spine and cervical facet joints, bone mineral density (BMD), vertebral fractures (VF) and serum markers of bone resorption, formation, and mineralization during 2 year of secukinumab treatment in AS patients in daily clinical practice. <h3>Methods</h3> In this explorative study, consecutive AS outpatients from the GLAS cohort who were treated with secukinumab for 2 years were included. Standardized follow-up visits were performed at baseline (before start of secukinumab) and after 3/6 months, 1 and 2 years of treatment. Bone-related outcome was assessed at baseline and after 2 years. Radiographs were blinded for patient characteristics and scored in chronological time order by 2 independent trained readers. Spinal radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS; 0-72) and cervical facet joint involvement according the 'de Vlam' method (0-15). Radiographic VF were assessed using the Genant method and bone mineral density (BMD) with DEXA. Serum levels of BTM reflecting collagen resorption, collagen formation and facilitation of bone mineralization (sCTX, PINP and BALP, respectively) were measured at all visits. BTM Z-scores were calculated using a healthy reference population to correct for the normal influence of age and gender. Bone-related outcomes were explored using descriptive statistics. Generalized estimating equations were used to analyze BTM over time within patients. <h3>Results</h3> In total, 17 AS patients were eligible for analyses; 53% were male, mean age was 46.6±14.6 years, 82% were HLA-B27 positive, mean ASDAS at baseline was 3.9±1.2, median CRP was 5 (IQR 3 - 26) mg/L, 53% were biological naïve, and median time between diagnosis and start of secukinumab was 5.0 (IQR 1.5-12.0) years. After 2 years of secukinumab treatment, mean ASDAS was 2.2±1.1. At baseline, median mSASSS was 3.3 (IQR 1.3 - 10.2). 10 patients had mSASSS and facet joint data available at baseline and 2 years. Median progression rate was 1.1 units in 2 years and 4 patients (40%) showed progression of ≥2.0 mSASSS units or ≥1 new syndesmophyte. At baseline, median facet joint score was 1.5 (IQR 0.0 - 2.8), with partial or complete ankylosis in 7 (8%) individual facet joints in 5 patients. Median progression rate was 0.5 and 6 (12%) facet joints in 4 patients showed progression to partial or complete ankylosis. At baseline, there were no signs of VF. One traumatic VF (grade 3) occurred during 2 years of follow-up. At baseline, median BMD Z-score (n=12) was -0.6 (-1.5 - -0.4) for the lumbar spine and -0.1 (-1.8 - 0.1) for the hip and BMD remained stable over time. Before secukinumab treatment, median sCTX, PINP and BALP Z-scores were +0.0, -0.60 and +1.2 SD, respectively. The course of sCTX and PINP did not change significantly during follow-up, BALP Z-scores, however, significantly decreased at 2 years compared to baseline (Figure 1). <h3>Conclusion</h3> This explorative study in daily clinical practice with assessments of both new bone formation and bone resorption in AS patients treated with secukinumab showed that there was low radiographic damage at baseline, with little change during 2 years of treatment. Serum BTM levels reflecting the actual bone turnover process corrected for normal influence of age and gender showed high BALP at baseline, indicative for mineralization, which decreased during 2 years of secukinumab treatment. <h3>Acknowledgements</h3> This study was supported by an investigator initiated research grant from Novartis. <h3>Disclosure of Interests</h3> Mark Siderius Consultant of: Novartis., Suzanne Arends: None declared, Freke Wink Consultant of: Janssen., Anneke Spoorenberg Consultant of: Abbvie, Pfizer, MSD, UCB, and Novartis., Grant/research support from: Abbvie, Pfizer, UCB.